Water → N-(2-{[(3R)-1'-(4-methoxyphenyl)-5'-oxo-1,3'-bipyrrolidin-3-yl]amino}-2-oxoethyl)-3-(trifluoromethyl)benzamide

HRID 562579Notes

Reaction equation

HRID 562579 reaction equation
O.[CH3:2][O:3][C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH2:14][CH:13]=[CH:12][C:11]2=[O:15])=[CH:6][CH:5]=1.[O:16]=[C:17]([NH:32][C@@H:33]1[CH2:37][CH2:36][NH:35][CH2:34]1)[CH2:18][NH:19][C:20](=[O:31])[C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:30])([F:29])[F:28])[CH:22]=1.[NH4+].[OH-]>CCOC(C)=O.CO>[CH3:2][O:3][C:4]1[CH:5]=[CH:6][C:7]([N:10]2[C:11](=[O:15])[CH2:12][CH:13]([N:35]3[CH2:36][CH2:37][C@@H:33]([NH:32][C:17](=[O:16])[CH2:18][NH:19][C:20](=[O:31])[C:21]4[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:28])([F:30])[F:29])[CH:22]=4)[CH2:34]3)[CH2:14]2)=[CH:8][CH:9]=1

Participants

7

Reactant 4

HCID 962WaterHCID 14923Ammonium HydroxideHCID 552671331-(4-methoxyphenyl)-1,5-dihydro-2H-pyrrol-2-oneHCID 59556069(R)-N-(2-oxo-2-(pyrrolidin-3-ylamino)ethyl)-3-(trifluoromethyl)benzamide

Product 1

HCID 16666559N-(2-{[(3R)-1'-(4-methoxyphenyl)-5'-oxo-1,3'-bipyrrolidin-3-yl]amino}-2-oxoethyl)-3-(trifluoromethyl)benzamideYield 21.5%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

A slurry of water (20 μL, 0.10 mmol), 1-(4-methoxyphenyl)-1,5-dihydro-2H-pyrrol-2-one (200 mg, 1.06 mmol) and N-{2-oxo-2-[(3R)-pyrrolidin-3-ylamino]ethyl}-3-(trifluoromethyl)benzamide (666 mg, 2.12 mmol) was heated to 90° C. overnight. The crude mixture was subjected to flash chromatography (1% NH4OH, 15% MeOH, EtOAc) to afford, as a mixture of diastereomers, N-(2-{[(3R)-1′-(4-methoxyphenyl)-5′-oxo-1,3′-bipyrrolidin-3-yl]amino}-2-oxoethyl)-3-(trifluoromethyl)benzamide as a white solid (115 mg, 21%). 1H-NMR (CDCl3) δ: 1.50-1.82 (m, 1H), 1.83-2.00 (m, 1H), 2.18-2.40 (m, 1H), 2.40-2.58 (m, 1H), 2.56-2.81 (m, 3H), 2.83-3.00 (m, 2H), 3.29-3.33 (m, 2H), 3.60-3.71 (m, 2H), 3.79 (s, 3H), 4.04-4.20 (m, 2H), 4.38-4.47 (m, 1H), 6.94 (m, 2H), 7.19-7.30 (m, 2H), 7.69-7.80 (m, 2H), 7.99 (d, J=7.8 Hz, 1H), 8.18 (s, 1H). MS m/z: 505 (M+1).

Sources & evidence

ORD record
ord-8726066e108b4eacbcd89ba3049471f0
Source dataset
uspto-grants-2011_11
Patent number
US08067415B2

Reaction notes

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